Orthomyxoviruses Part 1

  1. Outside of orthomyxoviruses
    • Simple on the outside
    • Linear, - ssRNA
    • Contain HA and NA surface proteins
  2. Genome of orthomxoviruses
    Have 6- different segments of genetic material, some coding for two things wit different reading frames or promoter sequences
  3. Proteins of the genome
    • Envelope glycoproteins: HA and NA
    • integral membrane protien: (M2)
    • Matrix protein (M1)
    • Nucleocapsid (NP)
    • nonstructural (NS1)
    • minor structural (NS2
    • additional non strutural (PB1-F2)
  4. Genes and proteins
    HA and NA are on two different gene segments

    3 proteins deal with the interstructure of the virus. they are viral RNA dependent polymerases that are made of different subunits
  5. What is the special case that must occur since it is negative sense
    at least one copy of an RNA pol has to be packaged in

    no polymerase= no infection
  6. There was a recently discovered...
    protein that can be made from PB2 segment

    really short peptide that is an open reading frame and has specific immune system effects
  7. Viruses and hosts
    these viruses affect mucus tisse and make you cause and sneeze
  8. Explain this: influenza has its own family tree
    • all differ in the HA and NA
    • A affects humans and mutates faster 
    • B affects humans and is a seasonal epidemic
    • C

    A and B are genetically differetn
  9. What sets influenza apart?
    high fever, sore throat, cough, headache, muscular pain

    incapacitation for about a week

    can be fatal in the elderly, infants, and chronically ill; complications--> death
  10. What is the trend for influenza?
    a classic U-shaped curve with age and fatality on the x and y axis, respectively

    at very young and old age, virus is deadly

    this trend exists for the regular annual flu
  11. Explain the two epidemics that were pretty bad
    1918: pandemic= 20 millino people dead

    2009: new strain; bird flu that threatened domestic fowl and humans
  12. Explain the trend of the 1918-1919 pandemic
    w shaped curve

    it affected overall life expectancy

    • more than 10,000 people died in a month
    • US military men died more of the flu than in combat
    • Everything else became secondary to surviving the infection

    mortality rate spiked in Oct and Nov

    rate of dying correlated to age; middle aged also at risk
  13. The Fle: seasonal versus pandemic
    seasonal: reliably, it kills alot of people and can be the number one killer of children in developing countries really affects young and elderly; fatality is 0.5%

    pandemic: deaths can be 4-5%
  14. Pandemic Influenza mortality
    The 1918 virus was so frightening because one minute you were fine, the next, you were dead
  15. Reasons for the pandemic
    viral genes: some strains are worse in humans

    WWI: lots of people in poor health and close quarters--> increased subsceptibility and transmission

    Poor understanding of disease
  16. Gram stains
    successful for getting stains in those with Spanish flu

    There was bacterial growth in the lungs of those infected, which usually caused the death

    95% of people that died from flu had positive bacterial infection association

    Bacteria may have evolved to take advantage of the niche
  17. Stability of flu?
    constantly mutating and changing, rendering immunity meaningless. Howver, it is cyclical
  18. Explain the cyclical nature of flu.
    IT comes and goes and comes back

    People in 1918 saw a flu that was similar to something their bodies have previously encountered, rendering them somewhat immune--> decrease in mortality
  19. Influenza virion
    • can take several forms
    • 1) if growing in person= long and filamentous (quasi-spherical is what you see in lab; filamentous is what you see in person)
  20. explain the different shapes of the virus?
    filaments help it come in contact with another cell while it is budding from one host membrane, transmitting it to another cell

    the spherical is how you can transmit to another person
  21. Genes and proteins again
    there is some space inside the virus around the genome segments, each of which has specific organizationa nd way of folding together

    a spin, a cube, and then proteins
  22. Three biggest genes?
    encode the segments for polymerase

    the smallest code for nonstructural
  23. Distinctive characteriSTICS
    A nuclear protein which resembles a green ball is not different from other nuclear proteins and wraps the RNA, whih loops up and back down
  24. Explain the polymerase
    it is in three different subsets, each having its own polymerase that is bound to it and brought with it

    PA, PB1, and PB2 all together wound up with loop structure and polymerase with it
  25. Most important (to us) protein on the virus?
    hemagglutinin protein: does both jobs that virus surface proteins need to do

    • 1) mediates fusion in endosomes
    • 2) binds to receptors
  26. HA binds to...
    a molecule called sialic acidin muclproteins

    each HA binds to different sialic acids
  27. What is hemagglutinin named after?
    • ability to cause hemagglutination
    • binds to RBCs, hemaggluniating agent causes RBCS to cross link and no longer clump and settle at the bottom. They stay in solution
  28. What is good about hemagglutinin?
    it is one of the most reliable sources of detecting infection

    • 1) Take serum
    • 2) Drop it in and mix with RBCS
    • 2) If hemagglutination occurs, the virus is present
  29. M2
    an ion channel that faciliates release of nucleocapsids from the virion

    It allows the protons to enter the interior of the virus weakening the interaction of M1 with the nucleocapsids

    Amantadine blocks the M2 channel
  30. Unlike other RNA viruses, what does orthomyxo do?
    it replicates in the nucleus, complicating the machinery required for viral replication
  31. The capped 5' ends of cellualr pre-mRNAs are used as __.
    • priers for synthesis of viral mRNAs
    • inhibitors of cellular RNA synthesis also blocks virus replciation

    It is a cap snatch
  32. Viral mRNAs terminate in __.
    poly(A) tail generated by "stuttering" transcription
  33. Explain alternative splicing in relation to influenza
    Two influenza A mRNAs undergo alternative splicing in the nucleus

    • -- unspliced RNAs create M1 and NS1
    • -- spliced RNAs create M2 and NS2
  34. When does genome rep begin?
    when newly synthesized NP protein enters the nucleus

    replication of genome requires no primer
  35. Nucleocapsids are __.
    exported from the nucleus in a complex with matrix protein and NS2
  36. The NS1 protein does what?
    interferes with polyadenylation of cellular mRNAs

    it binds to and blocks the function of cleavage and polymadenylation specificy factor (CPSF) and poly(A)-binding protein (PABII)
  37. The NS1 protein also....
    suppresses a variety of host cell antiviral response pathays

    • 1) inhibits RIG-I
    • 2) Activates P13K/Akt pathway
    • 3) Inhibits PKR
    • 4) Inhibits 2',5'-oligo(A) synthetaase/Ribonuclease L
  38. PB1-F2.....
    may contribute in suppression of host immune response

    localizes to mitochondria and induces apoptosis in host immune cells
Card Set
Orthomyxoviruses Part 1
Tset Two